Lung cancer is the leading cause of cancer death accounting for one third of all deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for ˜75-85% of all histotypes of lung cancer, small cell lung cancer (SCLC) accounting for the remainder. Despite extensive preclinical and clinical research, the overall prognosis for patients with NSCLC remains poor, with a 5-year survival rate of only 14%.
In recent years, knowledge concerning the molecular mechanisms underlying cellular transformation and development of cancer has been greatly expanded. Therapeutic agents have been discovered that target tyrosine kinase receptors, such as the ErbB receptors, which are involved in a variety of cancers, including lung cancer. In particular, agents that target the epidermal growth factor receptor (EGFR), an ErbB receptor, have been developed. While small molecule EGFR targeted therapies, including EGFR-tyrosine kinase inhibitors (TKI) ZD1839 (Iressa™) and erlotinib (Tarceva™), have displayed good initial clinical results, tumor cells frequently develop resistance over time and may become non responsive to the therapy. New approaches are needed to treat patients suffering from a cancer, such as NSCLC, that is not responsive to traditional TKI therapies.